[摘 要] 目的：检测lncRNA LOC440173在NSCLC组织和细胞中的表达及探讨其对癌细胞恶性生物学行为的影响。方法：选取河北医科大学第四医院生物标本库中2014至2017年手术切除的72例NSCLC患者的癌及癌旁组织标本，应用qPCR法检测NSCLC组织和癌旁组织中，以及6种NSCLC细胞株（H520、H358、A549、HCC827、H1703和H1299）中LOC440173的表达水平；构建LOC440173的敲低及过表达载体，分别转染H520和H1703细胞，应用MTS、克隆形成及Transwell小室迁移和侵袭实验分别检测敲低及过表达LOC440173对NSCLC细胞增殖、迁移及侵袭能力的影响，qPCR法检测LOC440173对于EMT过程相关标志物（E-cadherin、N-cadherin及vimentin）mRNA表达水平的影响，WB法检测其对E-cadherin、N-cadherin蛋白表达的影响。结果：LOC440173在NSCLC组织中的表达明显高于癌旁组织（P<0.01），并与淋巴结转移、组织学分化程度、TNM分期和肿瘤大小有关联（P<0.05或P<0.01）。敲低LOC440173可以抑制H520细胞的体外增殖、迁移和侵袭（P<0.05或P<0.01），过表达LOC440173可显著促进H1703细胞的增殖、迁移和侵袭（P<0.05或P<0.01）。在转录水平上，敲低LOC440173后，E-cadherin的表达水平升高，间充质相关标志物N-cadherin、vimentin的表达水平降低（P<0.05或P<0.01）；而过表达LOC440173后，E-cadherin的表达水平降低，间充质相关标志物N-cadherin、vimentin的表达水平升高（P<0.05或P<0.01）。在转录后水平上，LOC440173负向调节E-cadherin蛋白的表达、正向调节N-cadherin的蛋白表达（均P<0.05）。结论：LOC440173在NSCLC组织中的异常高表达可能与NSCLC的发生发展有关，LOC440173可显著提高NCSCL细胞的体外增殖、迁移、侵袭能力，且其作用机制可能与调控EMT相关基因表达有关。

BACKGROUND: Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring. METHODS: The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy. RESULTS: Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months. CONCLUSIONS The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.

Background and objective Non-small cell lung cancer (NSCLC) has been transformed from the treatment according to histological type to genotype treatment model. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes are the most important drivers in lung cancer. The aim of this study is to explore the clinical characteristics and prognostic factors of patients with advanced NSCLC with different genotypes. Methods We retrospectively reviewed the clinical data of 553 advanced NSCLC patients with EGFR mutations and ALK positive who were hospitalized in the Beijing Chest Hospital from July 2004 to December 2015, and the independent prognostic factors of pa-tients were analyzed by Cox proportional hazards regression model. Results The clinical data of 553 patients (227 with EGFR mutations, 58 with ALK positive, 2 with EGFR and ALK co-mutation and 266 with wild-type) with advanced NSCLC were enrolled in this study. The median survival time of 227 patients with EGFR mutations was 28.7 mo (95%CI: 22.160-35.240), and the performance status (PS) score (0-1) (HR=4.451; 95%CI: 2.112-9.382; P<0.001) and EGFR-tyrosine kinase inhibitors(TKIs) targeted therapy (HR=2.785; 95%CI: 1.871-4.145; P<0.001) were the independent prognostic factors for the survival of patients harboring EGFR mutations. The median survival time of 58 patients with ALK positive was 15.5 mo (95%CI:10.991-20.009), and treatment with crizotinib (P=0.022) was the independent influence factor for the survival of ALK positive patients. The median survival time of 266 patients with wild-type was 12.1 mo (95%CI: 10.660-13.540), and the PS score (0-1) (HR=2.313; 95%CI: 1.380-3.877; P=0.001) and treatment with chemotherapy (HR=1.911; 95%CI: 1.396-2.616; P<0.001) were the independent prognostic factors for the survival of wild-type patients. Conclusion The prognosis of patients with advanced NSCLC is associated with genetic mutation, and targeted therapy has a improvement on survival for patients with EGFR mutations or ALK rearrangement.

Background and objective Kirsten rat sarcoma viral oncogene (KARS) mutation is one of the major driver genes of non-small cell lung cancer (NSCLC). KARS is a resistant predictor of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which raises controversy because of its role in chemotherapy sensitivity and prognosis. hTe aim of this study is to accumulate clinical experience in treating NSCLC patients harboringKARSmutation.MethodsA total of 107 NSCLC patients harboringKARSmutation were analyzed retrospectively. hTe effcacy was analyzed in terms of ifrst-line chemotherapy or EGFR-TKIs therapy.Results hTe objective response rate (ORR) to ifrst-line chemotherapy of 52 pa-tients with advanced disease harboringKARS mutation was 9.6%. hTe disease control rate (DCR) was 53.8%, and the median progression-free survival (PFS) was 3 months. hTe ORR to EGFR-TKIs therapy in 21 patients harboringKARS mutation and EGFR/KARS co-mutation was 9.5%; the DCR was 23.8%, and the median PFS was 1 month. hTe ORR and DCR to EGFR-TKIs therapy of patients withEGFR/KARS co-mutation were signiifcantly higher than those of patients withKARS mutation (50%vs 0,P=0.029; 75%vs 11.8%,P=0.043); the median PFS was also signiifcantly longer (3 monthsvs 1 month,P=0.004). Conclusion hTe effcacy to ifrst-line chemotherapy and EGFR-TKIs therapy in NSCLC patients harboringKARS mutation was poor; thus, new drugs should be developed. Furthermore, the existence ofEGFR/KARS co-mutation was conifrmed. Hence, EGFR-TKIs therapy should be administered to patients withEGFR/KARS co-mutation.

Background and objectiveAnaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is an important subtype of lung cancer. hTe standard modality of ALK-positive NSCLC with brain metastases re-mains uncertain.MethodsWe collected data on clinical characteristics and treatment of patients with ALK-positive NSCLC and brain metastases between March 2013 and March 2016 and retrospectively analyzed patient outcomes.Results In 84 ALK-positive patients with advanced NSCLC, 22 (26.2%) had brain metastases during the initial diagnosis of lung cancer, among which 3 patients with EGFR mutation were excluded, and 19 patients were analyzed. Median intracranial progression-free survival (PFS) was 12.0 months. PFS for patients who received first-line local brain therapy (P=0.021) and crizotinib therapy (P=0.030) was superior to PFS for patients without such therapies. PFS for patients who received ifrst-line crizotinib combined with local brain therapy was 27.0 months and only 4.2 months for those who received crizotinib alone.Conclusion First-line crizotinib therapy combined with local brain treatment can improve intracranial PFS for ALK-positive NSCLC with brain metastases. hTis ifnding should be conifrmed further through multicenter, prospective clinical trials with large sample size.

Background and objective Status of epidermal growth factor receptor (EGFR) gene is a predictor of response to EGFR tyrosine kinase inhibitor (TKI). However, lile is know about the relationship between EGFR status and response to chemotherapy. We evaluated the prediction value of EGFR mutation status on response to first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods e data of 181 patients with stage IIIb/IV NSCLC who diagnosed by histopathology from January 10, 2006 to December 20, 2013 in Beijing Chest Hospital, Capital Medical University were collected. e relationships between EGFR gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed. Results All of the 181 patients’ EGFR statuses were determined. 75 (41.4%) patients har-bored EGFR-activating mutations and 106 (58.6%) patients were EGFR wild-type. All patients received first-line chemother-apy. e objective response rate (ORR) was 26.0% and disease control rate (DCR) was 70.2%. Patients with EGFR-activating mutations had a higher DCR than patients with EGFR wild-type (84.0% vs 60.4%, P=0.001) did. Subgroup analysis showed that the ORR and DCR in patients with EGFR exon 19 deletions were remarkably higher than those with EGFR wild-type (P= 0.049, 0.002, respectively). e DCR in patients with EGFR exon 21 L858R mutation was significantly higher than that in patients with EGFR wild-type (P=0.010). 168 patients were available for response evaluation in all of 181 patients and median PFS was 4.3 mo. e PFS of patients with adenocarcinoma was significantly higher than that patients with squamous cell carci-noma (4.7 mo vs 3.0 mo, P=0.036). e PFS in patients harbored EGFR-activating mutations was significantly higher than that in the patients with EGFR wild-type (6.3 mo vs 3.0 mo, P=0.002). e PFS of patients with a performance status (PS) of 0-1 was significantly higher than that in patients with a PS of 2 (4.4 months vs. 0.7 months, P= 0.016). Cox multivariate analysis indicates the EGFR-activating mutation is an independent factor aecting PFS (HR=0.654, 95%CI: 0.470-0.909, P=0.012). Conclusion EGFR-activating mutation is a predictor for PFS of first-line chemotherapy in advanced NSCLC patients.

Background and objective Activating mutations in epidermal growth factor receptor (EGFR) and KARS are important markers in non-small cell lung cancer. However, EGFR and KARS gene mutations in lung squamous cell carcinoma are rarely reported. hTe aim of this study was to analyze EGFR and KARS gene mutation rate and their relationship with clinical features in patients with lung squamous cell carcinomas. Methods A total of 139 patients undergoing treatment for na?ve lung squamous cell carcinomas with tumor tissue samples available for testing were recruited. EGFR and KARS mutation statuses of the tumor samples were detected using a mutant enriched liquid chip. Results Of the 139 cases of lung squamous cell carcinoma, EGFR mutations were detected in 25 cases (18%), KARS mutations were detected in 7 cases (5%), and the pres-ence of both EGFR and KARS mutations was detected in 1 case (0.7%). EGFR mutations occurred more otfen in females than in males (33.3%vs 16.5%) and in patients that never smoked than in those who smoke (29.6%vs 16.1%). However, the differ-ence did not reach statistical signiifcance (P>0.05). No signiifcant differences were observed in age, stage, and different biopsy type. KARS mutations occurred more otfen in males than in females (5.5%vs 0%), but the difference did not reach statistical signiifcance (P>0.05). No signiifcant differences were observed in age, stage, different biopsy type, and smoking status (P>0.05). Conclusion EGFR and KARS mutations were low in lung squamous cell carcinomas, and had no signiifcant correlation with clinical features. Before using tyrosine kinase inhibitor targeted therapy, EGFR and KARS mutations should be detected in pa-tients with lung squamous cell carcinomas.

Background and objectiveMutations in epidermal growth factor receptor (EGFR) andKARS are im-portant markers in non-small cell lung cancer, which are closely related to the clinical therapeutic effect. To analysis theEGFR andKARS gene mutation rate and its relationship with clinical features in patients with lung adenocarcinoma.Methods395 patients with treatment na?ve lung adenocarcinoma, tumor tissue samples were available for testing. Tumor sampleEGFR and KARS mutation status were detected using mutant enriched liquidchip.Results 395 cases of lung adenocarcinoma,EGFR mutations were detected in 192 cases (48.9%),KARS mutations were detected in 29 cases (7.8%), and the presence ofEGFR andKARS mutation were detected in 1 case (0.3%).EGFR mutations were found to occur signiifcantly more otfen in female than in male patients (62.0%vs 37.1%,P<0.001) and in never smokers than in smokers (61.9%vs 30.3%,P<0.001), no sig-niifcant differences were observed in age, stage and different biopsy type.KARS mutations were not found to have statistical signiifcance (P>0.05) in each clinical factors, only occurred in the wild typeEGFR gene in patients (13.5%, 27/200) was sig-niifcantly higher than that of patients withEGFR mutation (1.0%, 2/192), the difference was statistically signiifcant (P<0.001). ConclusionIn lung adenocarcinomas,EGFR mutation was higher in female and non-smoking patients,KARS mutation only in patients with wild-typeEGFR gene was higher. Before using TKI targeted therapy,EGFR andKARS mutations should be detected.

Background and objectiveIcotinib is the ifrst self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, geiftinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the effcacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients withEGFR mutation and wild-type.MethodsPatients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014.Re-sults hTe clinical data of 124 patients (99 withEGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. hTe patients’ overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; hTe patients withEGFR mutation, ORR was 63.6%, DCR was 93.9%. hTe ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment inEGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. hTe major adverse events were mild skin rash (30.6%) and diarrhea (16.1%).Conclusion Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLCEGFR mutation patients.

OBJECTIVE: To evaluate the efficacy of personal sublingual immunotherapy (SLIT) with dermatophagoides to study the efficacy of dermatophagoides farinae drops for allergic rhinitis (AR) of different age groups. METHOD: The current study had analyzed the efficacy of SLIT in 150 patients with AR who were sensitized to house dust mites. All patients were treated with dermatophagoides farinae drops and combined with symptomatic treatment. The patients were divided into groups 1-5, group 1:17 patients (4-7 years old), group 2: 38 patients (> 7-12 years old), group 3:31 patients (> 12-18 years old), group 4: 38 patients (> 18 - 40 years old), group 5: 26 patients (> 40-63 years old). The total nasal symptom scores (TNSS) and total medicine scores (TMS) were recorded at each visit. Before and after SLIT for 0.5 year, 1 year and 1.5 to 2.0 years, the TNSS and TMS of each patient were evaluated. The dosage adjustment of immunotherapy according to the patient's symptoms were performed. RESULT: The TNSS and TMS had continuously improved significantly after SLIT for half year, 1 year and 1.5 to 2.0 years in all groups as compared with baseline (P < 0.05). There were no significant differences in the different age groups for TNSS and TMS during all time points. CONCLUSION Individualized SLIT with dermatophagoides farinae drops for 1.5-2.0 years is the most effective in the patients with allergic rhinitis of different age groups. And equivalent efficacy could be achieved for different age groups.
Adolescent ; Adult ; Age Factors ; Animals ; Antigens, Dermatophagoides ; administration & dosage ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Rhinitis, Allergic ; therapy ; Sublingual Immunotherapy ; Treatment Outcome ; Young Adult